Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979-03-28 to 1979-05-03
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP study performed according to a method equivalent to OECD Guideline 402. Only 2 animals per sex and per dose tested instead of 5 as recommended in the OECD Guideline 402.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 2 animals per sex and per dose tested instead of 5 as recommended in the OECD Guideline 402
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Details described in study specific records
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4236-21-35
- Substance type: Clear colorless liquid
- Physical state: Liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Marland Breeding Farms, Inc., Hewitt, N.J.
- Age at study initiation: unknown
- Weight at study initiation: 2.5 to 3.1 kg

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
The hair of each rabbit was clipped from the trunk so as to expose at least 10% of the body surface area. The skin of half of the animals (4 males, 4 females) was abraded longitudinally every 2 or 3 centimeters so as to penetrate the stratum corneum but not so deep as to disturb the derma or produce bleeding.

REMOVAL OF TEST SUBSTANCE
Following 24 hours of exposure, the sleeves were removed and observations were made for edema, erythema and eschar formation. The exposed area was then wiped free of excess test material.

TEST MATERIAL
The test material was administered as received. The dose levels were calculated based on the density of the test material which was provided by the sponsor as being 0.944 g/mL.

The test material was held in contact with the skin by an 8-ply gauze wrapping and a sleeve made of impervious plastic sheeting designed to contain the dose without leakage or undue pressure. Collars designed to prevent the ingestion of the test material were worn by all animals throughout the study.
Duration of exposure:
24 hours
Doses:
2000, 2800, 4000 and 5600 mg/kg
The dose levels were calculated based on the density of the test material which was provided by the sponsor as being 0.944 g/mL.
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded initially, on day 7 and at the termination of the study (day 14)
- Necropsy of survivors performed: yes: A gross necropsy was performed on spontaneous deaths.
- Observations for mortality and overt signs of effect were made at 0-2 and 4-6 hours following dosing, and daily thereafter for fourteen days.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Based on:
test mat.
95% CL:
2 200 - 4 400
Mortality:
at 2000 mg/kg: 0/4 animals died
at 2800 mg/kg: 2/4 animals died
at 4000 mg/kg: 2/4 animals died
at 5600 mg/kg: 4/4 animals died
Clinical signs:
At the twenty-four hour dermal observation the majority of the animals at all levels exhibited severe erythema accompanied by necrotic skin and moderate edema.
Physical signs noted in the majority of animals at all dose levels during the fourteen-day post-dose observation period were clear nasal discharge, piloerection and motor activity decrease.
Body weight:
During the two-week observation period the majority of the surviving animals showed no change in weight or a slight weight gain.

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
The dermal LD50 of the substance was estimated to be 3300 mg/kg with 95% confidence limits of 2200 to 4400 mg/kg. The substance is not to be classified according to the CLP Regulation